We are studying a group of slow virus diseases of the central nervous system which are collectively referred to as the transmissible spongiform encephalopathies. The members of this group include two animal diseases, scrapie and transmissible mink encephalopathy, and two diseases of humans, Kuru and Creutzfeldt-Jakob disease. All of these diseases are characterized by an insidious onset after an incubation period of several months or years. There follows a clinical course of progressive loss of nervous function leading to complete debilitation and death. The pathologic alterations of all four diseases are similar, the main lesions being an intense reactive astrocytosis and spongiform degeneration of the gray matter caused by local cytoplasmic swellings in nerve cells and their processes. These diseases appear to be caused by closely related, nonconventional viruses which produce no detectable specific antibody responses, no recognizable cytopathologic changes in cell culture sytems, and have never been positively visualized. The objectives of our research are to: (1) isolate and characterize the etiological agent(s) of scrapie and transmissible mink encephalopathy, (2) study the pathogenesis of the animal encephalopathies in suitable hosts, and (3) study the etiological and epidemiological intrarelationships between the animal and human encephalopathies.